Proliferative vitreoretinopathy (PVR) is the principal cause of failed retinal reattachment surgery. Uncontrolled proliferation can lead to scar formation in the eye following surgical procedures. The resulting scar can result in visual impairment. We have designed ribozymes targeting PCNA mRNA that are capable of inhibiting cellular proliferation. In the Phase I portion of this work, we demonstrated that the PCNA targeted ribozymes were able to recognize and cleave the rabbit PCNA substrate. The ribozymes could be delivered into a variety of cell types involved in PVR development. Delivery of the ribozymes into the rabbit eye effectively inhibited the development of PVR in the rabbit dispase model. In this portion of the proposal, an optimized formulation for opthalmic use will be tested. The toxicity profile of the PCNA targeted ribozymes in the rabbit and porcine eye will be determined. These results will provide the foundation for development of this anti-proliferative drug for the treatment of PVR and for use in other surgical procedures in the eye with adverse outcomes due to ocular scarring. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE